U.S. patent application number 10/871458 was filed with the patent office on 2004-11-25 for transparent transdermal nicotine delivery devices.
Invention is credited to Gale, Robert M..
Application Number | 20040234585 10/871458 |
Document ID | / |
Family ID | 27381223 |
Filed Date | 2004-11-25 |
United States Patent
Application |
20040234585 |
Kind Code |
A1 |
Gale, Robert M. |
November 25, 2004 |
Transparent transdermal nicotine delivery devices
Abstract
A transparent transdermal delivery device for delivering
nicotine which has an Opacity Index of less than 48.6%
Inventors: |
Gale, Robert M.; (Los Altos,
CA) |
Correspondence
Address: |
PHILIP S. JOHNSON
JOHNSON & JOHNSON
ONE JOHNSON & JOHNSON PLAZA
NEW BRUNSWICK
NJ
08933-7003
US
|
Family ID: |
27381223 |
Appl. No.: |
10/871458 |
Filed: |
June 18, 2004 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
10871458 |
Jun 18, 2004 |
|
|
|
09464305 |
Dec 15, 1999 |
|
|
|
60112730 |
Dec 18, 1998 |
|
|
|
60124679 |
Mar 16, 1999 |
|
|
|
60126798 |
Mar 30, 1999 |
|
|
|
Current U.S.
Class: |
424/449 ;
514/343 |
Current CPC
Class: |
A61K 47/34 20130101;
A61K 9/7023 20130101; A61P 25/34 20180101; A61K 31/465 20130101;
A61K 2800/262 20130101; A61K 9/0014 20130101; A61K 9/7084 20130101;
A61K 47/32 20130101; A61K 9/703 20130101; A61K 31/4465
20130101 |
Class at
Publication: |
424/449 ;
514/343 |
International
Class: |
A61L 015/16; A61K
009/70; A61K 031/4439 |
Claims
We claim:
1. A device for the transdermal administration of nicotine
comprising a backing layer, a drug reservoir layer containing
nicotine carried by said backing layer, and means for maintaining
the device in nicotine transmitting relationship with the skin,
wherein the device is sufficiently transparent to permit the skin
of the subject to which it is applied to be visible through said
device.
2. The device of claim 1 wherein said backing has a nicotine
permeability of less than about 1.0 .mu.g/cm.sup.2
.multidot.hr.
3. A device according to claim 1 wherein the backing has a nicotine
permeability of less than 0.5 .mu.g/cm.sup.2 .multidot.hr.
4. A device according to claim 2 wherein the backing has a
solubility for nicotine of less than about 1 wt %.
5. A device according to claim 3 wherein the backing has a
solubility for nicotine of less than about 0.1 wt %.
6. A device according to claim 4 wherein the device has an Opacity
Index less than about 48.6%.
7. A device according to claim 6 wherein the device has an Opacity
Index of less than 35.11%.
8. A device according to claim 6 wherein the device has an Opacity
Index of less than 20%.
9. The device of claim 1 wherein said backing is formed from a
material selected from the group consisting of PET/EVA laminates,
HDPE/EAA/nylon/EAA multilaminate and a film comprising a graft
copolymer formed from about 73-77% acrylonitrile and from about
23-27% methyl acrylate copolymerized in the presence of about 8-10
parts by weight of butadiene/acrylonitrile copolymers containing
approximately 70% by weight of polymer units derived from
butadiene.
Description
CLAIM OF PRIORITY The inventor claims the benefit of the filing
date of provisional applications S. No. 60/112,730; 60/124,679 and
60/126,798.
FIELD OF THE INVENTION
[0001] The present invention relates to transdermal delivery
devices for administering nicotine for use in smoking cessation
treatments. In particular, the invention is directed to transdermal
nicotine delivery devices which are transparent.
BACKGROUND OF THE INVENTION
[0002] The transdermal route of parenteral drug delivery provides
many advantages over other administration routes. Transdermal
systems for delivering a wide variety of drugs or other beneficial
agents are described in U.S. Pat. Nos. 3,598,122; 3,598,123;
3,731,683; 3,797,494; 4,031,894; 4,144,317; 4,201,211; 4,286,592;
4,314,557; 4,379,454; 4,435,180; 4,559,222; 4,568,343; 4,573,995;
4,588,580; 4,645,502; 4,698,062; 4,704,282; 4,725,272; 4,781,924;
4,788,062; 4,816,258; 4,849,226; 4,904,475; 4,908,027; 4,917,895;
4,938,759; 4,943,435; 5,004,610; 5,071,656; 5,122,382; 5,141,750;
5,284,660; 5,314,694; 5,342,623; 5,411,740; and 5,635,203, which
are hereby incorporated in their entirety by reference.
[0003] The administration of nicotine buccally, nasally and
transdermally to assist a patient desiring to quit smoking has been
shown to be clinically effective in reducing the rate of
recidivism. Nicotine chewing gum and transdermal nicotine are two
of the most widely used forms of nicotine replacement therapy
currently available. Transdermal devices for administering nicotine
are disclosed in U.S. Pat. Nos. 4,597,961; 4,758,434; 4,764,382;
4,839,174; 4,908,213; 4,915,950; 4,943,435; 4,946,853; 5,004,610;
5,016,652; 5,077,104; 5,230,896; 5,411,739; 5,462,745; 5,508,038;
5,599,554; 5,603,947 and 5,726,190, for example, which are hereby
incorporated in their entirety by reference.
[0004] Most of the transdermal drug delivery devices of the prior
art utilize an impermeable backing on the skin distal surface of
the device to protect the device from damage and to prevent loss of
the active ingredient(s). In order to improve user satisfaction,
these backing layers are often tinted to a color similar to skin
tones. However, as can be readily appreciated, it is not
commercially practical to provide pigmented backing layers for
transdermal systems which approximate all skin colors.
[0005] Another approach that has been taken is to provide
transparent transdermal systems in which all elements forming a
device are sufficiently transparent to permit the natural skin
color to be visible through the device. Marketed products which
take this approach include the Alora.RTM. and Climara.RTM. estrogen
replacement patches and the Duragesic.RTM. transdermal fentanyl
delivery system. When these devices are applied to the skin, the
patient's natural skin color is visible through the patch, making
the presence of the patch extremely inconspicuous. Government
regulations require that these products bear identifying indicia,
but the indicia can be printed on these devices in light colored or
white ink which is not noticeable from a distance of several feet,
but is still readable on close inspection.
[0006] Such transparent patches have been found useful with
non-volatile drugs such as fentanyl and hormone replacement
steroids, but no such transparent product has been developed for
the delivery of nicotine.
[0007] Nicotine is a liquid alkaloid that is colorless, volatile,
strongly alkaline, readily oxidized, subject to degradation on
exposure to light and highly permeable through not only the human
skin, but also many of the polymers conventionally used in the
fabrication of backing layers and packaging materials for
transdermal products (see for example U.S. Pat. No. 5,077,104). As
a result, the backing layers of the transdermal nicotine delivery
devices currently available utilize opaque, skin-colored
multilaminate films which typically contain a metallized layer,
such as aluminum.
[0008] Not only do the commercially available transdermal nicotine
patches use opaque backings, but many of these devices, due to the
complexities of handling and processing nicotine, have other
components which are not transparent. For example, the original
Prostep.RTM. transdermal nicotine product used a drug reservoir in
the form of an opaque white gel, held in place by an opaque
adhesive overlay. The Habitrol.RTM. and Nicotrol.RTM. nicotine
patches incorporated absorbant pads in the drug reservoir in which
the nicotine was absorbed.
[0009] It has also been proposed to co-administer nicotine with
other substances that improve nicotine cessation therapy. See, for
example, U.S. Pat. Nos. 4,908,213; 5,599,554; and 5,726,190 noted
above, and WO 97/33581.
SUMMARY OF THE INVENTION
[0010] The present invention relates to transparent transdermal
delivery devices for the transdermal administration of nicotine,
either alone or in combination with other agents.
[0011] Such devices should be sufficiently transparent so that the
subject's skin can be clearly visible through the device when it is
placed on the skin. Identifying indicia can be printed on the
device in light colored or white ink in a manner which is not
noticeable from a short distance, but is readable on close
inspection.
DETAILED DESCRIPTION OF THE INVENTION
[0012] Preferred devices of this invention utilize, as the backing
layer, a transparent polymeric film which has a permeability to
nicotine of less than 1 .mu.g/cm.sup.2.multidot.hr, preferably less
than 0.5 .mu.g/cm.sup.2.multidot.hr, a solubility for nicotine that
is less than 1% by weight and preferably less than 0.1%. Such films
are preferably less than about 6 mils thick and most preferably
about 2-4 mils thick. Such films are used in combination with one
or more of the conventional elements of a transdermal device (other
than the removable release liner) such as the drug reservoir,
adhesive and rate controlling membranes, which must also be
sufficiently transparent as to permit the natural skin color to be
clearly visible through the assembled device after placement on the
skin. The finished product should have an Opacity Index of less
than about 48.6%, preferably less than about 35.11% and more
preferably less than 20%.
[0013] In addition to being transparent and being sufficiently
impermeable to nicotine, the backing layer must also have
sufficient mechanical strength and physical integrity to maintain
the system intact throughout its intended administration period,
which is typically 18-24 hours, and must provide a stable interface
with adjoining layers such as the drug reservoir or adhesive layers
of the transdermal device. This combination of properties is not
always found in one material, and thus the transparent backing
layers used on the devices of this invention can be multilaminate
films. In addition to having a low permeability to nicotine, a
backing layer must also have a low solubility for nicotine. This is
because nicotine is toxic and it could be dangerous for a child,
for example, to lick the backing layer if it contained a
substantial amount of dissolved nicotine.
[0014] Suitable polymer materials possessing properties required by
this invention include Scotchpak.RTM. 1220 which is a polyethylene
terephthalate/ethylene vinyl acetate (PET EVA), bilaminate film
sold by the 3M Company, Minneapolis, Minn. and Saranex.RTM. 2057
which is a high density polyethylene (HDPE)/ethylene acrylic acid
(EM)/nylon/EM multilaminate available from the Dow Chemical
Company, Midland, Mich. Nitrile rubber graft copolymers with
acrylonitrile and methyl acrylate sold as Barex.RTM. films
described in U.S. Pat. No. 5,077,104 noted above, can also be
used.
[0015] These films, comprising a graft copolymer formed from about
73-77% acrylonitrile and from about 23-27% methyl acrylate
copolymerized in the presence of about 8-10 parts by weight of
butadiene/acrylonitrile copolymers containing approximately 70% by
weight of polymer units derived from butadiene are preferred
backing materials.
[0016] The transparent transdermal delivery devices of this
invention can be of any of the forms described in the
aforementioned patents. The preferred form, however, comprises a
laminate of the backing layer, a nicotine reservoir layer which
contains nicotine dissolved in a carrier at a concentration below
the saturation concentration of nicotine in the carrier. If the
drug reservoir component is self adhesive, a simple monolithic
device could be employed. However, in many cases it is desirable to
include additional components such as rate controlling membranes,
and a separate adhesive layer for maintaining the devices on the
skin such as is described in U.S. Pat. Nos. 5,004,610 and 5,342,623
listed above. It is further contemplated that in addition to
nicotine, the device may also contain other drugs or other active
substances which cooperate with or enhance the effect of nicotine
in smoking cessation, smoking replacement or smoking substitution
therapy. For all these devices, a removable release liner would
normally be applied on the adhesive surface of the patch that is
used to keep the device on the skin, which release liner is removed
prior to use.
[0017] Various materials suited for fabrication of the various
components are known in the art and are disclosed in the
aforementioned patents.
[0018] The adhesive component is preferably a pressure sensitive
adhesive including, but not limited to, polysiloxanes,
polyacrylates, polyurethanes, acrylic adhesives including cross
linked or uncross linked acrylic copolymers, vinyl acetate
adhesives, ethylene vinylacetate copolymers, and natural or
synthetic rubbers including polybutadienes, polyisoprenes, and
polyisobutylene adhesives, and mixtures and graft copolymers
thereof. The devices may also be provided with hydrophilic water
absorbing polymers known in the art such as polyvinyl alcohol and
polyvinyl pyrolidone individually or in combination. The adhesive
can be used to form a monolithic delivery device in which the
nicotine is dissolved in the adhesive to form a self-adhesive drug
reservoir. Alternatively, the adhesive can be applied to the
surface of a non-adhesive reservoir in which nicotine is dissolved,
to form a multilaminate device. A rate-controlled membrane can also
be interfaced between the nicotine reservoir and the adhesive, as
is known to the art.
[0019] The nicotine can be administered in combination with another
agent which could include anti-anxiolytics, antihypertensives,
antidepressants, and appetite suppressants, such as fluoxetine,
caffeine, buspirone, phenylpropanolamine, clonidine, paroxetine,
citalopram, and sertraline.
[0020] The nicotine in the device is present in the reservoir at a
subsaturated condition (i.e. less than unit activity) such that no
undissolved nicotine is present in the reservoir. If other agents
are present in the device, they are preferably present fully
dissolved, but can be present in undissolved form so long as the
end product displays the proper degree of transparency.
[0021] In the present invention, nicotine and optionally other
agents to be co-administered are delivered through the skin or
other body surface at a therapeutically effective rate for a
predetermined time period which for nicotine is preferably 16-24
hours.
[0022] The transdermal therapeutic devices of the present invention
are prepared in a manner known in the art, such as by those
procedures described in the transdermal device patents listed
previously herein.
[0023] The following example is offered to illustrate the practice
of the present invention and is not intended to limit the invention
in any manner.
EXAMPLE 1
[0024] Various commercially available transdermal patches were
tested to determine their transparency and compared to the
transparent nicotine patches according to this invention. The
nicotine patches were prepared as set forth in Example IV of U.S.
Pat. No. 5,004,610 with a PET/EVA (Scotchpak.RTM. 1220, 3M,
Minneapolis, Minn.) or Saranex.RTM. (Dow Chemical Company, Midland,
Mich.) backing substituted for the Scotchpak 1006 backing. The
light transmitted through the various systems was measured by a
Macbeth 1500/Plus color measurement system (Kollmorgem Instruments
Corp., Newburgh, N.Y.). Table 1 shows the Opacity Index, which is
the percentage of incidental light which is absorbed by passage
through the device, for the various systems tested.
1TABLE 1 Patch Opacity Patch Opacity Index Minitran .RTM. 48.6%
Alora .RTM. 20.21% FemPatch .RTM. 35.11% Climara .RTM. 19.33% Ex. 1
- Nicotine with Saranex .RTM. backing 17.04% Ex. 1 - Nicotine with
PET/EVA backing 19.66%
[0025] The Minitran.RTM. nitroglycerine system is clearly visible
from a distance of about 5 feet, whereas the FemPatch.RTM. is
significantly less noticeable. The Alora.RTM., Climara.RTM. and
Nicoderm.RTM. patches, however, are extremely inconspicuous.
Accordingly, transdermal devices according to this invention should
have an Opacity Index less than 48.6%, preferably less than 35.11%,
more preferably less than 20%.
[0026] Having thus generally described our invention and preferred
embodiments thereof, it is apparent that various modifications and
substitutions will be apparent to workers skilled in the art. These
modifications and substitutions can be made without departing from
the scope of our invention which is limited only by the following
claims.
* * * * *